DTIC ADA418031: Medical Ultrasound Technology Research and Development at the University of Washington Center for Industrial and Medical Ultrasound

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1 . AGENCY USE ONLY (Leave Blank) 2. REPORT DATE 3. REPORT TYPE AND DATES COVERED

2 October 2003 Final (07/01/99 - 06/30/03)

4. TITLE AND SUBTITLE

Medical Ultrasound Technology Research and Development at the University of
Washington Center for Industrial and Medical Ultrasound

5. FUNDING NUMBERS

N000 14-99- 1-0982

6. AUTHOR(S)

Lawrence A. Crum

7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)

Applied Physics Laboratory
University of Washington
1013 NE 40th St.

Seattle, WA 98105-6698

9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES)

Office of Naval Research
800 N. Quincy St.

Arlington, VA 22217-5660

Attn: Dr. Michael Given, Code 341

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Approved for public release

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AGENCY REPORT NUMBER

20031106 083

13. ABSTRACT (Maximum 200 words)

This grant provided support to expand the scientific program and infrastructure at the University of Washington’s Center
for Industrial and Medical Ultrasound (CIMU). The many disparate facilities and technical capabilities available to
CDVTU staff and students were integrated and enhanced to provide a world-class, advanced research center for
bioengineering development and graduate education in high-intensity, focused ultrasound (HIFU). This included
leveraging of overall research in understanding of acoustic hemostasis and improvement of research tools. Significant
progress was made in developing a highly automated transducer characterization capability. Features include acoustic
field mapping by scanned hydrophones, acoustic power efficiency measurement, electric and acoustic impedance
measurement, medical ultrasound imaging and RF data collection, optical methods of acoustic field mapping (Schlieren
apparatus), and for each system a convenient software interface and user manual. Specialized fixtures and instruments
were developed to measure HIFU dose response in vitro , an essential component of developing reliable and realistic
computer models for HIFU simulation and treatment planning. Single-element HIFU transducers were refined with
liquid, gel, and solid coupling media and other improvements to be more powerful, convenient, and robust. These
technological enhancements have enabled the development of HIFU arrays and image-guided ultrasound systems for
greater flexibility and control in clinical treatment protocol. Lastly, significant bioacoustic model development was
undertaken for use in practical engineering design as well as for fundamental research of the mechanisms of ultrasound
therapy.

14. SUBJECT TERMS

acoustic hemostasis, bioacoustic, bioengineering, hemorraghic trauma, high-intensity focused ultrasound
(HIFU), ultrasound

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17

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FINAL TECHNICAL REPORT FOR ONR GRANT N0001 4-99-1 -0982
" MEDICAL ULTRASOUND TECHNOLOGY RESEARCH AND DEVELOPMENT AT
THE UNIVERSITY OF WASHINGTON CENTER FOR INDUSTRIAL AND

MEDICAL ULTRASOUND"

Lawrence A. Crum, Principal Investigator

I. Background

This grant supported a research effort to understand more fully the basic science issues that
comprise High Intensity Focused Ultrasound (HIFU) technology, and to build the basis for
more expansive development of this general technology. Specific areas on interest included
the use of HIFU in the treatment of hemorrhagic trauma and related pathological conditions,
especially in organs that are difficult to treat using conventional medical and surgical
techniques. Direct applications include combat casualty care, as well as many civilian uses
in non-invasive or minimally invasive trauma management, bloodless surgery, and
ultrasound-mediated drug therapy. Research efforts also explored imaging and simulation
techniques associated with treatment, targeting and monitoring the effectiveness of HIFU
therapy. A significant portion of the grant was directed toward renovation of laboratory
spaces to enable the research efforts described above. The period of performance of the grant
was from 1 Julyl999 to 30 June 2003.

II. Accomplishments

A. Executive Summary

This grant provided support to expand the scientific program and infrastructure at the
University of Washington (UW) Center for Industrial and Medical Ultrasound (CEMU). The
broad objectives falling within this scope included:

• To understand more fully the physical and biological mechanisms that give rise to
acoustic hemostasis and HIFU surgical lesion production.

• To develop techniques for the utilization of gas-filled ultrasound contrast agents in
the detection and localization of bleeding.

• To develop and validate theoretical models of acoustic hemostasis and HIF U surgical
lesion production.

• To develop techniques for the real-time monitoring of HlF U-induced lesions in tissue.

• To develop additional laboratory transducer designs that produce acoustic hemostasis
and HIF U lesions, and to extend these laboratory designs toward engineering
prototypes.

• To understand more fully and to optimize the physical and biological mechanisms
that give rise to ultrasound-mediated drug delivery.

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During the performance period the many disparate facilities and technical capabilities
available to CIMU staff and students were integrated and enhanced to provide a world-class,
advanced research center for HIFU bioengineering development and graduate education.
Program funds were used to leverage overall research efforts in understanding of acoustic
hemostasis and improve research tools. Significant progress was made in developing a
highly automated transducer characterization capability, including providing dedicated
instrumentation and facilities for this purpose. Features include acoustic field mapping by
scanned hydrophones, acoustic power efficiency measurement, electric and acoustic
impedance measurement, acoustic and material parameter measurement, medical ultrasound
imaging and RF data collection, optical methods of acoustic field mapping (Schlieren
apparatus), and for each system a convenient software interface and user manual. Specialized
fixtures and instruments were developed to measure HIFU dose response in vitro, an
essential component of developing reliable and realistic computer models for HIFU
simulation and treatment planning. Single element HIFU transducers were refined with
liquid, gel, and solid coupling media and other improvements to be more powerful,
convenient, and robust. These technological enhancements have enabled the development of
HIFU arrays and image-guided ultrasound systems for greater flexibility and control in
clinical HIFU treatment protocol. Lastly, significant bioacoustic model development was
undertaken for use in practical engineering design as well as for fundamental research of the
mechanisms of ultrasound therapy.

B. R&D Facilities Improvements

A significant portion of this grant was directed toward renovation of laboratories to support
research efforts at the newly created Center for Industrial and Medical Ultrasound. Space
was acquired in the University of Washington Old Fisheries Center (OFC), conveniently
located near the UW’s Medical Center and Health Sciences buildings, but facilities
improvements were urgently needed. Working in careful coordination with facilities crews
from both the Applied Physics Laboratory and Main Campus, the best possible use was made
of renovation funds provided under this grant.

One of the major benefits of the laboratory renovation has been to create good quality
laboratory facilities that are proximal to the clinical facilities i.e. the UW Medical School and
Medical Center. This location allows clinicians to be able to interact with the laboratories and
still be closely available to their clinical duties. This becomes increasingly important as
diagnostic and therapeutic ultrasound projects involve more clinical input. It is also more
convenient for the subjects/patients. The proximity of the location to the Dept, of Radiology
is particularly important for projects such as vascular ultrasound where input is needed on
imaging and image guided therapy. The ultrasound patient studies laboratory (OFC room
119) provides specially-needed facilities for obtaining 3D images, eg. a non-magnetic
environment for image registration.

Other highlights of the renovation efforts are described and illustrated in the following
paragraphs.

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OFC Room 102N: Joint Imaging Laboratory

This laboratory was the most significantly in need of repair, as it contained unidentified
chemicals, discarded nonfunctional equipment, and peeling lead-based wall and fixture paint.
Lead-based paint abatement was completed, new paint applied, and the rusted countertops
were sanded and buffed; before and after photographs are shown in Figure 1. This lab now
serves as the joint imaging lab, used by multiple investigators working on new ultrasound
imaging and detection algorithms, and systems integration for image-guided therapy.

Figure 1. OFC Room 102N, the CIMU Joint Imaging Laboratoi

OFC Room 112: Ultrasound Biophysics Laboratory

This laboratory was completely remodeled to serve as an ultrasound bioeffects laboratory for
both in vitro and in vivo experimentation. It had been a radiation biophysics lab with
extremely limited peripheral bench surfaces, no work surface in the center of the room, worn-
out wooden cabinetry, and very low quality water supply. The original walls contained
asbestos, which required significant abatement efforts. The laboratory now features modem
steel cabinetry, spacious bench areas, including a sizable central island affording unrestricted
access to large and complex experimental setups (or animals) from all sides, and providing a
great deal of flexibility with respect to equipment configuration. All surfaces are clad in

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impermeable materials and can be chemically disinfected to remove either potentially
biohazardous contaminants or to prepare surfaces for animal research. Abundant 120 V (and
one 220 V) power drops were installed overhead to permit the use of a large number
electronic instruments without encumbering the work surfaces with power cords. The lab
now has two spatially separate sink areas (one dedicated to conventional use, and the other
dedicated to disposal of biohazardous fluids and initial decontamination of equipment
exposed to biohazardous fluids). A high quality water purifier has been installed. Basic
utilities (gas, compressed air) are available in a large fume hood used for various chemical
procedures. The lab is equipped with instrumentation for transducer
characterization/exposimetry, apparatus for sonication of in vitro and in vivo biological
specimens, a dual-beam spectrophotometer, a small drying oven, and is amenable to general
chemistry operations (preparation of gel phantoms, etc.). See Figure 2 for photographs
during and following the renovation.

_ Completed renovation _

Figure 2. OFC Room 1 12, the CIMU Ultrasound Biophysics Lab

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OFC Room 114: Tissue Culture/Media Preparation Lab

This laboratory is composed of a larger outer room, and two small inner rooms. The outer
room and one of the two inner rooms have been renovated; the second inner room was left
unaltered since its primary purpose is to storage voluminous tissue culture supplies and other
consumables. Photographs are shown in Figure 3. The second small inner room, which
required lead-liner removal, was transformed into a dedicated tissue culture facility. Installed
features include wall-mounted cabinetry for sterile supply storage, a small sink and base
cabinet and a drawer unit with disinfectable work surface. The room houses a laminar flow
hood for aseptic transfers, a C02 incubator, a Coulter Z1 particle counter, a clinical
centrifuge, vacuum pump, and water bath. The renovated outer room contains a central
island work bench, a sink and base cabinet, and several wall-mounted cabinets for glassware
storage. The principal purpose of this room is for media preparation, but it was also designed
to accommodate in vivo studies of small animals. Installed equipment includes an old but
serviceable fume hood (existing), an ice machine, and a small autoclave for sterilization of
tissue culture supplies and the degassing of water for use in ultrasound tanks. Appliances or
mobile equipment/supply items include a refrigerator (media and/or biological specimen
storage), balances, pH meters, chemical storage cabinet and salts, etc.

OFC Room 125: CIMU In Vitro/Ex Vivo Studies Laboratory

This room was also completely renovated, having had only exposed concrete walls and floors
and primary use as a storage area - see Figure 4. This room is located in the western wing of
the building, near the CIMU ultrasound patient studies and systems development
laboratories. Room 125 now is used by all CIMU staff and students to conduct bench top, in
vitro experiments, involving tissue characterization, tissue-mimicking phantom production,
and transducer fabrication. It also houses a wall-mounted water distiller that is heavily used
by CIMU staff and students working in this far wing of the building. A small refrigerator
provides chemical storage.

OFC Room 102M: CIMU Ultrasonic Characterization Laboratory
This room required minor renovations, including installation of plumbing and a small sink,
new paint, new power and communications conduit, and custom curtains for the optical
studies area. A photograph of the workspaces is provided in Figure 5. The laboratory is used
by all staff and students to conduct transducer radiation force, field mapping and schlierin
optical measurements. In vitro and ex vivo HEFU dose response and lesion monitoring
studies are also conducted in this laboratory.

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C. Research Efforts

As indicated above, this grant enabled the integration of many disparate facilities and
technical capabilities to provide advanced acoustic research spaces for HIFU bioengineering
development and graduate education. A summary the research highlights from this project is
outlined below. This list of graduate student theses supported by this grant is provided in

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section II.D. A complete bibliography of research papers and presentations funded by or
relevant to this grant is provided in section II.F.

C.l Modeling Efforts

A 2-D full-wave, fully nonlinear acoustic model was developed as part of a Ph.D. student's
dissertation (see Curra under the list of student theses in Section II.F). This type of model is
considered the “gold standard,” and can be used to benchmark other, particularly
approximate models, and to perform the most complete theoretical investigations into the
physical and biological mechanisms of HIFU therapy. Full-wave models are highly
complex, and thus require both significant computing resources as well as computing time.
To reduce computational intensity, efforts also were directed toward the development of an
approximate field model, in particular an implementation of a nonlinear parabolic wave
equation (the KZK equation). These models have been used to perform simulation studies to
support HIFU transducer design and protocol development.

C.2 Transducer Design Studies

During the course of this grant significant progress was made toward developing a highly
automated transducer characterization capability with dedicated instrumentation and facilities
for this purpose. New capabilities include acoustic field mapping by scanned hydrophones,
acoustic power efficiency measurement, electric and acoustic impedance measurement,
acoustic and material parameter measurement, medical ultrasound imaging and RF data
collection, optical methods of acoustic field mapping (Schlieren apparatus), and for each
system a convenient software interface and user manual. Specialized fixtures and instruments
were also developed to measure HIFU dose response in vitro, which forms an essential
component of in the verification and development of reliable and realistic computer models
for HIFU simulation and treatment planning. Single element HIFU transducers were refined
with liquid, gel, and solid coupling media and other improvements to be more powerful,
convenient, and robust. These various technological enhancements have enabled further
development of HIFU arrays and image-guided ultrasound systems for greater flexibility and
control in clinical HIFU treatment protocol.

C.3 HIFU Monitoring Efforts

Efforts in developing HIFU monitoring techniques were focused on two efforts. The first
component focused on using B-mode diagnostic imaging to monitor lesion evolution. This
type of monitoring is possible because lesions formed by HIFU are hyperechoic for several
seconds after treatment; CIMU studies using overpressure indicate mild cavitation is
responsible for the echogenicity in the focal region. At low intensity levels the HIFU focus
can be observed using interleaved B-mode imaging for a brief time (1 second or less) without
causing permanent damage (i.e. no lesions were found in acute studies at such exposures).
This feature enabled targeting with low HIFU exposures before applying HIFU at full
treatment levels. Then, by interleaving HIFU therapy with diagnostic ultrasound
interrogation, the focal region can be imaged and monitored during therapy application. This
effort represents a major thrust of CIMU Image Guided Therapy (IGT) development.

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The second monitoring component focused on developing new signal processing algorithms
using the raw Radio Frequency (RF) ultrasound backscatter data from a diagnostic ultrasound
machine, in this case the HDI-1000 developed by ATL, Inc., in Bothell, WA. Significant
treatment information, including tissue motion and tissue temperature, can be obtained from
the RF ultrasound data. This research effort was initiated during the latter part of the
performance period and is being completed under other grants.

C.4 HIFU Bioeffects Studies

In order to understand more frilly how tissue properties change with HIFU treatment, studies
were conducted in which the bulk properties of ultrasound attenuation and sound speed were
measured before and after HIFU treatment. These demonstrated that ultrasound attenuation
increases after HIFU treatment, whereas the speed sound remains statistically the same.
These results are useful in developing treatment protocols and optimizing parameters for
image-guided HIFU systems.

Instrumentation was developed to study quantitative in vitro dose response and to use in
careful comparison with numerical simulations of HIFU therapy. In vitro dose response
studies were initiated during the latter part of this grant and have continued under other
funding vehicles. Of particular interest is investigating the threshold below which results a
purely thermal effect and above which results in thermal and mechanical effects, in particular
acoustic and/or vaporous cavitation.

HIFU-induced biological mechanisms leading to hemostasis in solid organs and in vascular
wounds were investigated, and this effort has continued via funding from other projects.
Research was directed specifically at understanding how the tissue emulsion produced during
surgical treatment in intraoperative studies is formed and why it aids hemostasis.

C. 5 Contrast Agent Studies

These studies occurred during the early part of the grant and focused on contrast agent
microbubble behavior in an ultrasound field. Bubble destruction thresholds, inertial
cavitation thresholds, and bubble dissolution rates were studied for a variety of contrast
agents. This effort has evolved into a major area of study which is now funded by the
National Institutes of Health.

D. Degrees and Fellowships Conferred

The following individuals earned degrees through funding provided in whole or in part by
this project

• Francesco Curra, Ph.D., 2001, dissertation title “Medical Ultrasound Algorithm for
Noninvasive High Intensity Ultrasound Applications.”

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• Jonathan Yuen, M.S., 2001, thesis tittle "Characterization of lesion formation in a
tissue- mimicking phantom for focused ultrasound surgery."

• Sandra Poliachik, Ph.D., 2002, dissertation title “An Investigation of the Mechanisms
of High Intensity Focused Ultrasound Induced Platelet Activity."

• Tyrone Porter, Ph.D., 2003, dissertation title, “An investigation of the synergy
between ultrasound and membrane-disruptive polymers and its effect on cell
membranes.”

The following individual’s Post-Doctoral Fellowship was funded in part by this project:

• Dr. Cyril Lafon.

The following student is continuing research efforts that were initiated under this project:

• Ajay Anand, Ph.D. candidate, dissertation title “A Model-Based Noninvasive
Temperature Estimation Technique for H1FU Therapy Monitoring Using
Backscattered Ultrasound.”

E. Intellectual Property

One invention disclosure was filed at the University of Washington: 2031-3433 Medusa
Version 1.0. The form DD 882, Report of Inventions and Disclosures, will be forward
separately from the UW Office of Technology Licensing.

F. Publications

Refereed Journal Articles
Refereed Articles - 2000

Brayman AA (Section Leader), Delecki D, Wible J, Wu J, Abramowicz JS, Meltzer RS, and
Porter TR. Mechanical bioeffects in the presence of gas-carrier ultrasound contrast agents.
In: Fowlkes JB, Holland CK, eds.. Mechanical Bioeffects From Diagnostic Ultrasound:
Consensus Statements. J Ultrasound Med 2000; 19(2): 120-142.

Chang PP, Chen WS, Mourad PD, Poliachik SL and Crum LA. Thresholds for inertial
cavitation in Albunex suspensions under pulsed ultrasound conditions. IEEE Transactions on
Ultrasonics, Ferroelectrics, and Frequency Control 2000; 48(1): 16 1-170.

Curra FP, Mourad PD, Khokhlova VA, Cleveland RO, and Crum LA. Numerical simulations
of heating patterns and tissue temperature response due to high intensity focused ultrasound
fields. IEEE Trans UFFC 2000; 47(4): 1077-1089.

Dunmire B, Beach KW, Labs K, et al. Cross-beam vector Doppler ultrasound for angle-
independent velocity measurements. Ultrasound Med Biol 2000; 26(8): 1213-1235.

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Kwok C, Mourad P, Crum L, and Ratner B. Surface modification of polymeric slab surfaces
with self-assembled monolayer and is characterization with multi-surface-analytical
techniques. Biomacromolecules 2000; 1(1), pp. 139-148.

Miller MW, Sherman TS, and Brayman AA. Comparative sensitivity of human and bovine
Erthrocytes to sonolysis by 1 MHz ultrasound. Ultrasound Med Biol 2000; 26:1317-1326.

Refereed Articles - 2001

Bailey MR, Couret LN, Sapozhnikov OA, Khokhlova VA, ter Haar G, Vaezy S, Shi X,
Martin R, and Crum LA. Use of overpressure to assess the role of bubbles in focused
ultrasound lesion shape in vitro. Ultrasound Med Biol 2001 May; 27(5): 695-708.

Chang PP, Chen WS, Mourad PD, Poliachik SL, and Crum LA. Thresholds for inertial
cavitation in albunex suspensions under pulsed ultrasound conditions. TF.F.F. Trans Ultrason
Ferroelectr Freq Control 2001; 48(1): 161-70.

Lafon C, Kaczkowski PJ, Vaezy S, Noble M, and Sapozhnikov OA, “Development and
characterization of an innovative synthetic tissue-mimicking material for high intensity
focused ultrasound (HIFU) exposures,” IEEE Ultrasonics Symposium, 2, 1295 -1298 (2001).

Mourad PD, Lazar DA, Curra FP, Mohr BC, Andrus KC, Avellino AM, McNutt LD, Crum
LA, and Kliot M. Ultrasound accelerates functional recovery after peripheral nerve damage.
Neurosurgery 2001; 48(5): 1136-41.

Mourad PD, Murthy N, Porter TM, Poliachik SL, Crum LK, Hoffman AS, Stayton PS.
Focused ultrasound and poly(2-ethylacrylic acid) act synergistically to disrupt lipid bilayers
in vitro. Macromolecules 2001; 34(8): 2400-2401.

Poliachik SL, Chandler WL, Mourad PD, Olios RJ, Crum LA. Activation, aggregation and
adhesion of platelets exposed to high-intensity focused ultrasound. Utrasound Med Bio 2001;
27(11):1567-1576.

Porter T, Crum L, Stayton P, Hoffman A, “Sonoporation of Erythrocytes by Combination of
Synthetic Polymer and Ultrasound,” In: Proc. 17th International Congress on Acoustics
(Rome, Italy, Sept 2-7, 2001).

Shi X, Martin RW, Vaezy S, Kaczkowski P, and Crum LA. Color Doppler detection of
acoustic streaming in a hematoma model. Ultrasound Med Biol 2001; 27(9): 1255-64.

Vaezy S, Martin RW, and Crum LA. Acoustic Surgery. Physics World 2001; 14(8): 35-39.

Vaezy S, Martin RW, and Crum LA. High intensity focused ultrasound: a method of
hemostasis. Echocardiography 2001; 18(4): 309-15.

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Vaezy S, Shi XG, Martin RW, Chi E, Nelson PI, Bailey MR, and Crum LA. Real-time
visualization of high-intensity focused ultrasound treatment using ultrasound imaging.
Ultrasound Med Biol 2001 ;27(1): 33-42.

Refereed Articles - 2002

Anand AJ, Kaczkowski PJ, Daigle RE, Huang L, Paun M, Beach KW, and Crum LA, “Using
the ATL HDI-1000 ultrasound scanner to collect demodulated RF data for monitoring HIFU
lesion formation,” Proc SPIE, 5035, 316-326 (2003).

Curra FP, Kargl SG, and Crum LA, “Parameter space investigation of optimal thermal lesion
generation in noninvasive HIFU applications,” in Therapeutic Ultrasound. Proceedings of the
2nd International Symposium. M.A. Andrew, L.A. Crum and S. Vaezy, eds (American
Institute of Physics Press), pp. 275-281 (2003).

Refereed Articles - 2003

Anand AJ, Kaczkowski PJ, “Monitoring formation of High Intensity Focused Ultrasound
(HIFU) induced lesions using backscattered ultrasound”, Acoustic Research Letters Online,
August 2003 (submitted).

Curra FP and Crum LA, "Therapeutic ultrasound: Surgery and drug delivery," Acoustic
Science and Technology, 24, 6 (2003).

Poliachik SL, Chandler, WL, Olios RJ, Bailey MR, and Crum, LA, “The Relation Between
Cavitation and Platelet Aggregation During Exposure to High Intensity Focused Ultrasound,”
Ultrasound Med Biol , accepted, (2003).

Books or Book Chapters

Andrew MA, Crum LA, and Vaezy S (editors), Proceedings of the 2nd International
Symposium on Therapeutic Ultrasound, University of Washington, Seattle, Washington,
2003.

Crum, L.A., K. Beach, S. Carter, W. Chandler, F. P. Curra, P. Kaczkowski, G. Keilman, V.
Khokhlova, R. Martin, P. D. Mourad, and S. Vaezy (2000) Acoustic Hemostasis. In: W.
Lauterbom and T. Kurz, (eds.), "Nonlinear Acoustics at the Turn of the Millennium." Am.
Inst. Of Physics, ISNA 15, (New York), pp. 13-22.

Crum LA, Bailey M, Carter S, Curra F, Kaczkowski P, Kargl S, “Image-guided acoustic
hemostasis,” in New Acoustics: Selected Topics. C. Ranz-Guerra and J. A. Gallego- Juarez,
eds., (Consejo Superior de Investigaciones Cientificas, Madrid), pp 26-36 (2002).

D. A. Lazar, F. P. Curra, B. C. Mohr, L. D. McNutt, M. Kliot and Mourad, P. D.,
“Acceleration of recovery after injury to the peripheral nervous system via ultrasound and
other therapeutic modalities”. In Neurosurgery Clinics of North America -Peripheral Nerve

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Issues: Controversies and Evolving Treatments-. M. Kliot editor, W. B. Saunders Publishing
House, April 2001.

Vaezy, S. Martin RW, Kaczkowski P, Keilman G, Goldman B, Yaziji H, Carter S, Caps M,
Crum LA: Use of High Intensity Focused Ultrasound to Control Bleeding. Yearbook of
Vascular Surgery 2000.

Vaezy S, Andrew M, Kaczkowski P, and Crum L. Image-guided acoustic therapy. Annu
Rev Biomed Eng 2001 ; 3: 375-90.

Technical Reports

Mourad, P.D. and S.G. Kargl (2000) Acoustic Properties of Fluid-Saturated Blood Clots.
APL-UWTR2003.

Student Theses

Curra, F, "Medical Ultrasound Algorithm for Noninvasive High Intensity Ultrasound
Applications" - Ph.D. Dissertation, University of Washington, August, 2001.

Poliachik, S. "An Investigation of the Mechanisms of High Intensity Focused Ultrasound
Induced Platelet Activity," Ph.D. Dissertation, University of Washington, 2002.

Porter, T., “An investigation of the synergy between ultrasound and membrane-disruptive
polymers and its effect on cell membranes”

Yuen, J, "Characterization of lesion formation in a tissue- mimicking phantom for focused
ultrasound surgery," M.S. Thesis, University of Washington, December, 2001.

Abstracts. Posters & Presentations

Abstracts & Presentations - 2000

Crum L, Bailey M, Carter S, Curra F, Kaczkowski P, Kargl S, Martin R, Mourad P, and
Vaezy S, "Image-guided Acoustic Hemostasis." Symposium on Architectural Acoustics , II
Ibero-American Congress of Acoustics, XXXI National Congress of Acoustics -
TECNIACUSTICA 2000-, II Ibero-American Meeting on Ultrasonic and II Iberian Congress
of Acoustics, Madrid, Spain, 16-20 October 2000

Curra FP, Mourad PD, Khokhlova VA, and Crum LA, "3D full wave ultrasonic field and
temperature simulations in biological tissue containing a blood vessel." 139th Meeting of the
Acoustical Society of America, Atlanta,GA, May 30-June 3, 2000

Curra FP, Mourad PD, Kargl SG, and Crum LA, “Theorectical predictions of ultrasound
fields, temperature response, and lesion dynamics in biological tissue for the purpose of
noninvasive disease treatment,” J. Acoust. Soc. Am, 108, 2546 (2000).

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Lafon C, Bailey M, Couret L, Kaczkowski P, Sapozhnikov O, Brayman A, Crum L. Real¬
time observation of inception and growth of HIFU-induced tissue lesions. J. of Acous. Soc.
of Am., Newport Beach, USA, 2000;108:2546.

Martin R, Vaezy S, Shi X, Kaczkowski P, paun M, Beach K, and Crum L (2000) "Real-Time
Visualization of Therapeutic Ultrasound: Applied to Acoustic Hemostasis," 9th Congress of
the World Federation for Ultrasound in Medicine and Biology, Florence Italy.

Mourad, P.D., D.A. Lazar, F.P. Curra, B. Mohr, K.C. Andrus, A.M. Avellino, L.D. McNutt,
L.A. Crum and M. Kliot, Ultrasound accelerates functional recovery after peripheral nerve
damage, 9th International Meeting of the World Federation of Ultrasound in Medicine and
Biology , Florence, Italy, 6-10 May, 2000.

Poliachik SL, Chandler WL, Mourad PD, Olios RJ, Crum LA. Effect of high-intensity
focused ultrasound on platelet aggregation, activation and adhesion. Institute of Cancer
Research Joint Department of Physics, Royal Marsden Hospital, Surrey England, 26 April
2000.

Poliachik, SL, Chandler, WL, Mourad, PD, Olios, RJ, Crum, LA. Effect of high-intensity
focused ultrasound on platelet aggregation, activation and adhesion. 9th Congress of the
World Federation for Ultrasound in Medicine and Biology, Florence, Italy, 6-10 May 2000.

Poliachik SL, Chandler WL, Mourad PD, Olios RJ, Crum LA. Effect of high-intensity
focused ultrasound on platelet aggregation, activation and adhesion. 139th Meeting
Acoustical Society of America, Atlanta, GA, 31 May 2000.

Poliachik SL, Chandler WL, Mourad PD, Olios RJ, Crum LA. Activation, Aggregation and
Adhesion of Platelets Exposed to High Intensity Focused Ultrasound. 2000 IEEE
Ultrasonics Symposium Proceedings; 2000; Vol. 2 pp. 1433-1436.

Poliachik, SL, Chandler, WL, Mourad, PD, Olios, RJ, Crum, LA. Platelet activity as a result
of exposure to high intensity focused ultrasound. 140th Meeting Acoustical Society of
America, Newport Beach, CA, 6 December 2000.

Porter, TM, Nickerson J, Crum LA, Black FE, Murthy N, Stayton PS, and Hoffman AS,
“Influence of chemical composition of membrane-disrupting polymers on relative cavitation
activity and hemolysis,” J Acoust Soc Am, 108 (5), Pt. 2, 2547 (2000).

Shi X, Martin R, Vaezy S, and Crum L (2000) Experimental Investigation and Finite
Element Simulation of Streaming in Blood in Cylindrical Models, IEEE International
Ultrasonics Symposium.

Vaezy S, Martin R, Shi X, Paun M, Beach K, Kaczkowski P, Keilman G, Carter S, Bailey M,
and Crum L (2000) Hemostasis of Catheter-Induced Femoral Artery Injuries using Image-
Guided Transcutaneous High Intensity Focused Ultrasound, Annual Biomedical Engineering
Society Meeting, Seattle, WA.

Page 15 of 17

Abstracts & Presentations - 2001

Bailey MR, Vaezy S, Yuen JC, Anand A, Miller NA, Kaczkowski PJ, and Crum LA.
Bubbles and acoustic image-guided high intensity focused ultrasound. 142nd Meeting
Acoustical Society of America, 3-7 December 2001, Fort Lauderdale, FL, J Acoust Soc Am
2001; 110: 2643.

Chen W, and Matula T. A light-scattering technique for investigating ultrasound contrast
agents. Session ID-5, p. 144. 2001 IEEE International Ultrasonics Symposium, 7-10
October 2001, Atlanta, GA

Crum LA. Acoustic hemostasis. Session 2H-3, p. 286. 2001 IEEE International Ultrasonics
Symposium, 7-10 October 2001, Atlanta, GA

Curra FP, Kargl SG, Lafon C, and Crum LA, “Theoretical predictions and experimental
results for non-invasive disease treatment via high intensity focused ultrasound: a
comparative study,” 17th International Congress on Acoustics 2001, Rome, Italy,
Biomedicine: Therapeutic Ultrasound , 4, 20-21 (2001).

Curra FP, Kargl SG, Lafon C, and Crum LA, “Thermal lesions produced by High Intensity
Focused Ultrasound: Theoretical predictions and experimental results,” Proc. of First
International Workshop on the Application of High Intensity Focused Ultrasound (H1FU) in
Medicine 2001, Chongqing, China, 29-31.

Curra FP, Kargl SG, Lafon C, and Crum LA, “High intensity focused ultrasound for non-
invasive disease treatment: Theoretical predictions and experimental results,” 141st Meeting
of the Acoustical Society of America, Chicago, IL, June 4-8, 2001, J Acoust Soc Am, 109
(5), p. 2457 (2001).

Dunmire B and Beach KW (2001). A brief history of vector Doppler. SPIEs International
Symposium Medical Imaging 2001, San Diego, CA, USA.

Dunmire B, Beach KW, Labs K-H, Paun M, Tschoeppel M (2001). Two-dimensional
velocity map of a normal femoral bifurcation, and its amplications for conventional pulsed
Doppler ultrasound. SPIEs International Symposium Medical Imaging 2001, San Diego,
CA, USA.

Dunmire B, Pagel G, Beach KW, Labs K-H (2001). Post stenotic flow distrurbances in a
steady flow model. SPIEs International Symposium Medical Imaging 2001, San Diego, CA,
USA.

Kaczkowski PJ, Vaezy S, Martin RW, and Crum LA. A multi-channel high-intensity
focused ultrasound system for image-guided therapy. J Acoust Soc Am 2001; 110: 2614.
142nd Meeting Acoustical Society of America, 3-7 December 2001, Fort Lauderdale, FL

Page 16 of 17

Lafon C, Vaezy S, Noble ML, Kaczkowski PJ, Martin RW, and Crum LA, “A new synthetic
tissue-mimicking phantom for high intensity focused ultrasound,” 17th International
Congress on Acoustics, Biomedicine: Therapeutic Ultrasound, 7, 32-33 (2001).

Lafon C, Vaezy S, Noble ML, Kaczkowski PJ, Martin RW, and Crum LA. A new synthetic
tissue-mimicking phantom for high intensity focused ultrasound. 17“* International Congress
on Acoustics 2001. Volume 4. Biomedicine. Therapeutic Ultrasound. Pp. 32-33. 17th
International Congress on Acoustics, 2-7 September 2001, Rome, Italy

Lafon C, Kaczkowski PJ, Vaezy S, Sapozhnikov OA, and Noble ML. Development and
characterization of an innovative synthetic tissue-mimicking material for high intensity
focused ultrasound (HIFU) exposures. Session P1J-2. P. 303. 2001 IEEE International
Ultrasonics Symposium,7-10 October 2001, Atlanta, GA

Lafon C, Sapozhnikov OA, Kaczkowski PJ, Vaezy S, Noble ML, and Crum LA. An
innovative synthetic tissue-mimicking material for high-intensity focused ultrasound. J
Acoust Soc Am 2001; 110: 2613. 142nd Meeting Acoustical Society of America, 3-7
December 2001, Fort Lauderdale, FL

Matula TJ, and Chen WS. A light-scattering technique for investigating ultrasound contrast
agents. 17th International Congress on Acoustics 2001. Volume 4. Biomedicine. Acoustics
in Medicine. Pp. 4-5. 17th International Congress on Acoustics, 2-7 September 2001, Rome,
Italy

Poliachik SL, Chandler WL, Olios RJ, and Crum LA. Role of high-intensity focused
ultrasound induced cavitation on platelet aggregation. 1701 International Congress on
Acoustics 2001. Volume 4. Biomedicine. Medical Ultrasound Bioeffects. Pp. 20-21. 17th
International Congress on Acoustics, 2-7 September 2001, Rome, Italy

Shi X, Martin RW, Vaezy S, and Kaczkowski PJ. Color Doppler imaging of acoustic
streaming for hematoma diagnosis. Session 1G-6. P. 261. 2001 IEEE International
Ultrasonics Symposium, 7- 10 October 2001, Atlanta, GA

Vaezy S. High intensity focused ultrasound for therapy in medicine. 17th International
Congress on Acoustics 2001. Volume 4. Biomedicine. Therapeutic Ultrasound. Pp. 2-3. 17th
International Congress on Acoustics, 2-7 September 2001, Rome, Italy

Vaezy S, Martin RW, and Crum LA. High intensity focused ultrasound for arrest of bleeding.
J Acoust Soc Am 2001; 110: 2643. 142nd Meeting Acoustical Society of America, 3-7
December 2001, Fort Lauderdale, FL

Abstracts & Presentations - 2002

Anand A, Huang L, Kaczkowski P, Daigle R, Crum L, “Using ATL HDI-1000 Ultrasound
Scanner for Tissue Elasticity Imaging,” Proceedings of the First International Conference on

Page 17 of 17

the Ultrasonic Measurement and Imaging of Tissue Elasticity, Niagara Falls, Ontario, Canada
(Oct. 2002).

Curra FP, Kargl SG, and Crum LA, “3-D Full Wave Ultrasonic Field and Temperature
Simulations in Inhomogeneous Biological Tissue,” Proceedings of the 16th International
Symposium on Nonlinear Acoustics 2002, Moscow, Russia, 19-23.

Curra FP, Kargl SG, and Crum LA, “Parameter space investigation of optimal thermal lesion
generation in noninvasive HIF'U applications,” in Therapeutic Ultrasound. Proceedings of the
2nd International Symposium. M.A. Andrew, L.A. Crum and S. Vaezy, eds (American
Institute of Physics Press), pp. 275-281 (2003).

Curra FP, Kargl SG, Lafon C, and Crum LA, ‘Theoretical predictions and experimental
results for non-invasive disease treatment via High-Intensity Focused Ultrasound: a
comparative study”, Proceedings of the 17th International Congress on Acoustics , Rome,
Italy, 2-7 September 2001.

Abstracts & Presentations - 2003

Anand AJ, Kaczkowski PJ, “Monitoring evolution of HIFU-induced lesions with
backscattered ultrasound”, 145th Meeting of the Acoustical Society of America, Nashville,
TN, April, 2003, J. Acoust. Soc. Am., Vol. 113, No. 4, Pt. 2, p 2310 (2003).

Anand AJ, Kaczkowski PJ, “Ultrasound RF-signal analysis of HIFU-induced
lesions”, Abstracts of 28th Ultrasonic Imaging and Tissue Characterization Symposium,
Arlington, VA published in Ultrasonic Imaging, Vol. 25 (1), Jan 2003.